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Canadian scientists find frequent structural changes of chromosomes in autism

Copy number alterations of genes contribute to autism in seven per cent
of cases
TORONTO, Jan. 17 /CNW/ - A Canadian team led by scientists at The
Hospital for Sick Children (SickKids) has discovered numerous chromosomal
regions containing autism spectrum disorder (ASD)-susceptibility genes. Gains
or losses of genes (referred to as copy number variation or CNV) were found in
seven per cent of the 400 autistic individuals examined. Additionally, a new
region was identified on chromosome 16 which conferred risk of ASD in one per
cent of families. These findings are published online today in the American
Journal of Human Genetics.
This study builds on results the group co-published in February of last
year in which genome-scanning methods were used to examine the genetic
architecture underlying autism susceptibility. "In this phase of our work we
applied even newer microarrays allowing us to better scrutinize DNA for CNV
changes in autism, and we focused on Canadian families because of the detailed
clinical information we've collected over the years," says Dr. Stephen
Scherer, the senior corresponding author of the study, senior scientist in
Genetics &amp; Genomic Biology at SickKids and professor of Molecular Genetics at
the University of Toronto. It was Scherer who discovered with others the
existence of CNVs as the most common form of genetic variation, including that
in some instances CNVs are involved in disease.
Autism is a complex developmental disorder found in roughly one in
165 children. ASD individuals exhibit impairments in reciprocal social
interaction and communication, and show a preference for repetitive,
stereotyped activities. Structural changes (CNV as well as translocation and
inversion of genes) along chromosomes have been identified in some individuals
with ASD, but the full etiologic role of these changes is unknown.
"Our finding that in seven per cent of families we find chromosome
changes in ASD children not seen in their parents has important clinical
implications," says co-author Dr. Peter Szatmari, director of the Offord
Centre for Child Studies, McMaster Children's Hospital, and head of Child
Psychiatry at McMaster University. "Our experience through this study
indicates that application of these new microarray-based genome scanning tests
may serve to focus clinical examination in a search for undetected syndromes
leading to ASD."
Dr. Wendy Roberts, head of the Autism Research Unit at SickKids and
developmental pediatrician at Bloorview Kids Rehab adds, "The new CNVs we
discovered on chromosome 16 in one per cent of our Canadian cohort are also
now described in two American studies in the New England Journal of Medicine
and Human Molecular Genetics by teams from Boston and Chicago, respectively."
According to Roberts, the Canadian team also found other families with
chromosome changes that overlap with some genes involved in other medical
genetic conditions such as velocardiofacial syndrome (chromosome 22q) and
mental retardation (chromosome 15q24 and 16p11.2), which in many cases led to
an identification or refinement of the diagnoses. "It will be important to
prepare for a demand for the new chromosome 16 and other tests, to understand
what the data really means, and to realize that the significance could be
quite different for each family requesting testing," adds Scherer.
Dr. Christian Marshall the lead author from SickKids notes, "Our genetic
data held many complexities reminiscent of ASD itself. But in a subset of ASD
cases we found at least six genes known to have a role in neuron function that
were not present in the typical two-copies found in the general population."
In addition to having potential clinical diagnostic importance these results
also help to further unlock the biological mysteries of why autism comes about
and what parts of the brain are involved.
The Canadian team partnered with scientists in Germany, The Netherlands,
and the U. S. on this study, and also works as part of an international autism
genetics consortium called the Autism Genome Project (AGP). The AGP began in
2002 when researchers from around the world decided to come together and share
their samples, data, and expertise to facilitate the identification of autism
susceptibility genes.
This research was supported by Genome Canada, The Centre for Applied
Genomics, Autism Speaks, Bloorview Kids Rehab, the Canada Foundation of
Innovation, the Canadian Institutes of Health Research (CIHR), the
GlaxoSmithKline-CIHR Pathfinder Chair in Genetics and Genomics at the
University of Toronto, the Canadian Institutes for Advance Research (CIFAR),
The Catherine and Maxwell Meighen Foundation, The W. Garfield Weston
Foundation, Ontario Genomics Institute, the McLaughlin Centre for Molecular
Medicine, the Lee K. and Margaret Lau Genetics Research Endowment Fund, the
McMaster Children's Hospital Foundation, the Netherlands Organization for
Scientific Research and the Royal Netherlands Academy of Arts and Sciences,
Ontario Innovation Trust, Ontario Ministry of Research and Innovation, the
National Alliance for Research on Schizophrenia and Depression (NARSAD), the
William Rosenberg Family Foundation, and the SickKids Foundation.
The Hospital for Sick Children (SickKids), affiliated with the University
of Toronto, is Canada's most research-intensive hospital and the largest
centre dedicated to improving children's health in the country. As innovators
in child health, SickKids improves the health of children by integrating care,
research and teaching. Our mission is to provide the best in complex and
specialized care by creating scientific and clinical advancements, sharing our
knowledge and expertise and championing the development of an accessible,
comprehensive and sustainable child health system. For more information,
please visit www.sickkids.ca. SickKids is committed to healthier children for
a better world.

For further information:

For further information: Janice Nicholson, Public Affairs, The Hospital
for Sick Children, (416) 813-6684, janice.nicholson@sickkids.ca